Skip to main content
. Author manuscript; available in PMC: 2020 Dec 8.
Published in final edited form as: Cancer Cell. 2020 Apr 13;37(4):530–542. doi: 10.1016/j.ccell.2020.03.006

Figure 1. Molecular Pathway Activation Downstream of BCR-ABL1.

Figure 1.

BCR-ABL1 dimerizes leading to autophosphorylation at tyrosine 177 of BCR. This serves as a docking point for the GRB2/GAB2/SOS complex which activates multiple signaling pathways, including PI3K/AKT and MAPK. Autophosphorylation of key residues in the BCR-ABL1 kinase domain also in turn activate the JAK/STAT pathway likely via activation of JAK2 and direct phosphorylation of STAT5. In the setting of BCR-ABL1 TKI resistance, extracellular growth factors can act via the JAK/STAT pathway to sustain cell growth. Leukemia stem cells may uniquely depend on WNT/β-catenin and SHH/SMO signaling for survival in the face of BCR-ABL1 kinase inhibition.